首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   197篇
  免费   19篇
  216篇
  2022年   3篇
  2021年   4篇
  2020年   3篇
  2019年   5篇
  2018年   5篇
  2017年   5篇
  2016年   6篇
  2015年   16篇
  2014年   16篇
  2013年   14篇
  2012年   19篇
  2011年   14篇
  2010年   11篇
  2009年   7篇
  2008年   16篇
  2007年   16篇
  2006年   14篇
  2005年   7篇
  2004年   10篇
  2003年   6篇
  2002年   7篇
  2000年   5篇
  1999年   2篇
  1994年   1篇
  1992年   1篇
  1991年   1篇
  1989年   1篇
  1982年   1篇
排序方式: 共有216条查询结果,搜索用时 0 毫秒
51.
Relating the effects of foraging niche variation to reproductive dynamics is critical to understand species response to environmental change. We examined foraging niche variations of the slender‐billed gull (Chroicocephalus genei), a nomadic colonial waterbird species during its range expansion along the French Mediterranean coast over a 16‐year period (1998–2013). We investigated whether range expansion was associated with a change in chick diet, breeding success, and chicks body condition. We also examined whether breeding success and chicks body condition were explained by diet and colonial characteristics (number of pairs, laying phenology, habitat, and locality). Diet was characterized using dual‐stable isotopic proxies (δ13C and δ15N) of feather keratin from 331 individuals subsampled from a total of 4,154 chicks ringed and measured at 18 different colonies. δ13C decreased and δ15N increased significantly during range expansion suggesting that chicks were fed from preys of increasing trophic level found in the less salty habitat colonized by the end of the study period. Niche shift occurred without significant change of niche width which did not vary among periods, habitats, or localities either. Breeding success and chick body condition showed no consistent trends over years. Breeding success tended to increase with decreasing δ13C at the colony level while there was no relationship between stable isotope signatures and chick body condition. Overall, our results suggest that even if range expansion is associated with foraging niche shift toward the colonization of less salty and more brackish habitats, the shift had marginal effect on the breeding parameters of the Slender‐billed gull. Niche width appears as an asset of this species, which likely explains its ability to rapidly colonize new locations.  相似文献   
52.
Mathematical modeling of the cardiac action potential has proven to be a powerful tool for illuminating various aspects of cardiac function, including cardiac arrhythmias. However, no currently available detailed action potential model accurately reproduces the dynamics of the cardiac action potential and intracellular calcium (Cai) cycling at rapid heart rates relevant to ventricular tachycardia and fibrillation. The aim of this study was to develop such a model. Using an existing rabbit ventricular action potential model, we modified the L-type calcium (Ca) current (ICa,L) and Cai cycling formulations based on new experimental patch-clamp data obtained in isolated rabbit ventricular myocytes, using the perforated patch configuration at 35-37°C. Incorporating a minimal seven-state Markovian model of ICa,L that reproduced Ca- and voltage-dependent kinetics in combination with our previously published dynamic Cai cycling model, the new model replicates experimentally observed action potential duration and Cai transient alternans at rapid heart rates, and accurately reproduces experimental action potential duration restitution curves obtained by either dynamic or S1S2 pacing.  相似文献   
53.
Bahn A  Hagos Y  Rudolph T  Burckhardt G 《Biochimie》2004,86(2):133-136
Protein sequence alignments revealed one amino acid position, where organic cation transporters (OCTs, aspartate (D) at position 475 of rOCT2) and organic anion transporters (OATs, arginine (R) at position 466 of rOAT1) are charged oppositely. To address the impact of this amino acid for protein function we cloned rat organic cation transporter 2 (rOCT2), the renal electrogenic cation transporter of the basolateral side of proximal tubule cells. Site-directed mutagenesis was used to generate rOCT2-D475R (rOCT2-mut). Heterologous expression of rOCT2 wild-type (rOCT2-wt) in A6 cells resulted in a significant uptake of the fluorescent organic cation 4-(4-dimethylaminostyryl)-N-methylpyridinium (ASP(+)). Accordingly, rOCT2-wt-transfected COS 7 cells showed an almost fourfold uptake of 25 microM [(14)C]-TEA, whereas rOCT2-mut did not exhibit any uptake of [(14)C]-TEA. These data indicate that rOCT2 transports both ASP(+) and TEA and that aspartate at position 475 of rOCT2 plays a critical role in transport function.  相似文献   
54.
Calcineurin is implicated in a myriad of human diseases as well as homeostasis and virulence in several major human pathogenic microorganisms. The fungus Aspergillus fumigatus is a leading cause of infectious death in the rapidly expanding immunocompromised patient population. Current antifungal treatments for invasive aspergillosis are often ineffective, and novel therapeutic approaches are urgently needed. We demonstrate that a mutant of A. fumigatus lacking the calcineurin A (cnaA) catalytic subunit exhibited defective hyphal morphology related to apical extension and polarized growth, which resulted in drastically decreased filamentation. The delta cnaA mutant lacked the extensive lattice of invading hyphae seen with the wild-type and complemented strains. Sporulation was also affected in the delta cnaA mutant, including morphological conidial defects with the absence of surface rodlets and the added presence of disjunctors creating long conidial chains. Infection with the delta cnaA mutant in several distinct animal models with different types of immunosuppression and inoculum delivery led to a profound attenuation of pathogenicity compared to infection with the wild-type and complemented strains. Lung tissue from animals infected with the delta cnaA mutant showed a complete absence of hyphae, in contrast to tissue from animals infected with the wild-type and complemented strains. Quantitative fungal burden and pulmonary infarct scoring confirmed these findings. Our results support the clinical observation that substantially decreasing fungal growth can prevent disease establishment and decrease mortality. Our findings reveal that calcineurin appears to play a globally conserved role in the virulence of several pathogenic fungi and yet plays specialized roles in each and can be an excellent target for therapeutic intervention.  相似文献   
55.
Genetic diversity of Poa annua in western Oregon grass seed crops   总被引:3,自引:0,他引:3  
The genetic diversity of Poa annua L.populations collected from western Oregon grass-seed fields was surveyed using 18 randomly amplified polymorphic DNA (RAPD) markers. Markers from 1357 individual plants from 47 populations collected at three sampling dates (fall, winter, and spring) for 16 sites were used to measure genetic diversity within and among populations. Site histories varied from low to high herbicide selection pressure, and some sites were subdivided by 3 years of differing post-harvest residue management. Gene diversity statistics, simple frequency of haplotype occurrence, and analysis of molecular variance (AMOVA) revealed the presence of significant variability in P. annua among sites, among collection dates within sites, and within collection dates. Nei gene-diversity statistics and population-differentiation parameters indicated that P. annua populations were highly diverse. Mean Nei gene diversity (h) for all 47 populations was 0.241 and total diversity (HT) was 0.245. A greater proportion of this diversity, however, was within (HS=0.209) rather than among (GST=0.146) populations. When populations were grouped by season of collection, within-group diversity was HS=0.241, while among-group diversity was GST=0.017. When populations were grouped by site, within-group diversity was HS=0.224, while among-group diversity was GST=0.087. The diversity among populations within season for fall, winter, and spring collections was GST=0.121, 0.142, and 0.133, respectively. Populations collected from fields with histories of high herbicide selection pressure showed low differentiation among collection dates, with GST as low as 0.016, whereas those collected from fields with low herbicide selection pressure showed greater differentiation among collection dates, with GST as high as 0.125. At high selection-pressure sites, populations were also lower in gene diversity (as low as h=0.155), while at low selection-pressure sites there was higher gene diversity (as high as h=0.286). The site to site variability was greater for the high selection-pressure sites (GST=0.107 or 69% of the total among-population variance), while the season of germination variability was greater at sites of low herbicide-selection pressure (GST=0.067, or 70% of the total among-population variance). High initial diversity coupled with a long-term re-supply of genotypes from the seed bank must have been factors in maintaining the genetic diversity of this weed despite the intensive use of herbicides. Knowledge of the genetic diversity of Willamette Valley P. annua should help in formulating more effective strategies for managing this weed. Received: 24 July 1999 / 11 November 1999  相似文献   
56.
While the mechanisms by which adult terrestrial plants deploy constitutive and induced responses to grazing pressure are well known, the means by which young aquatic plants defend themselves from herbivory are little studied. This study addresses nitrogen transport in the aquatic angiosperm Myriophyllum spicatum in response to herbivore exposure. Nitrogen tracers were used to monitor nitrogen uptake and reallocation in young plants in response to grazing by the generalist insect herbivore Acentria ephemerella. Total nitrogen content (N%) and patterns of nitrogen uptake and allocation (δ15N) were assessed in various plant tissues after 24 and 48 h. Following 24 h exposure to herbivore damage (Experiment 1), nitrogen content of plant apices was significantly elevated. This rapid early reaction may be an adaptation allowing the grazer to be sated as fast as possible, or indicate the accumulation of nitrogenous defense chemicals. After 48 h (Experiment 2), plants' tips showed depletion in nitrogen levels of ca. 60‰ in stem sections vulnerable to grazing. In addition, nitrogen uptake by grazed and grazing‐prone upper plant parts was reduced and nutrient allocation into the relatively secure lower parts increased. The results point to three conclusions: (1) exposure to an insect herbivore induces a similar response in immature M. spicatum as previously observed in mature terrestrial species, namely a rapid (within 48 h) reduction in the nutritional value (N%) of vulnerable tissues, (2) high grazing intensity (100% of growing tips affected) did not limit the ability of young plants to induce resistance; and (3) young plants exposed to herbivory exhibit different patterns of nutrient allocation in vulnerable and secure tissues. These results provide evidence of induced defense and resource reallocation in immature aquatic macrophytes which is in line with the responses shown for mature aquatic macrophytes and terrestrial plants.  相似文献   
57.
58.
A new strain of yellow‐green algae (Xanthophyceae, Heterokonta), tentatively named Heterococcus sp. DN1 (UTEX accession number UTEX ZZ885), was discovered among snow fields in the Rocky Mountains. Axenic cultures of H. sp. DN1 were isolated and their cellular morphology, growth, and composition of lipids were characterized. H. sp. DN1 was found to grow at temperatures approaching freezing to accumulate large intracellular stores of lipids. H. sp. DN1 produces the highest quantity of lipids when grown undisturbed with high light in low temperatures. Of particular interest was the accumulation of eicosapentaenoic acid, known to be important for human nutrition, and palmitoleic acid, known to improve biodiesel feedstock properties. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:853–861, 2013  相似文献   
59.
A novel series of α4β2 nAChR agonists lacking common pyridine or its bioisosteric heterocycle have been disclosed. Essential pharmacophoric elements of the series are exocyclic carbonyl moiety as a hydrogen bond acceptor and secondary amino group within diaza- or azabicyclic scaffold. Computer modeling studies suggested that molecular shape of the ligand also contributes to promotion of agonism. Proof of concept for improving working memory performance in a novel object recognition task has been demonstrated on a representative of the series, 3-propionyl-3,7-diazabicyclo[3.3.0]octane (34).  相似文献   
60.
mTOR is part of the PI3K/AKT pathway and is a central regulator of cell growth and survival. Since many cancers display mutations linked to the mTOR signaling pathway, mTOR has emerged as an important target for oncology therapy. Herein, we report the discovery of triazine benzimidazole inhibitors that inhibit mTOR kinase activity with up to 200-fold selectivity over the structurally homologous kinase PI3Kα. When tested in a panel of cancer cell lines displaying various mutations, a selective inhibitor from this series inhibited cellular proliferation with a mean IC50 of 0.41 μM. Lead compound 42 demonstrated up to 83% inhibition of mTOR substrate phosphorylation in a murine pharmacodynamic model.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号